Technical Abstract:
Pioneer studies on infectious disease and immunology by Jenner, Pasteur, Koch, Von Behring, Nocard, Roux, and Ehrlich forged a path for the dual-purpose with dual benefit approach, clearly demonstrating the relevance of veterinary studies for biomedical applications. Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and M. bovis in cattle, is an exemplary model for the demonstration of this concept. Early studies with cattle were instrumental in the development of the use of Koch’s tuberculin as an in vivo measure of cell-mediated immunity for diagnostic purposes. Calmette and Guerin demonstrated the efficacy of bacille Calmette Guerin (BCG, an M. bovis Nocard strain attenuated by serial passage) in cattle prior to use in humans as a vaccine. The interferon-gamma release assay, now widely used for TB diagnosis in humans, was developed for use in the Australian bovine TB eradication program, circa 1990. More recently, experimental infection and vaccine efficacy studies with cattle have demonstrated a correlation of vaccine-elicited central memory (TCM) and IL-17 responses to protective efficacy, robust gamma-delta T cell responses to mycobacterial antigens upon infection, correlation of specific antibody to mycobacterial (antigen) burden and lesion severity, anti-mycobacterial activity of CD4+ T cells via granulysin production, and an association of SIRPalpha+ cells with ESAT-6:CFP10-elicited multinucleate giant cell formation. Additionally, positive prognostic indicators of bovine TB vaccine efficacy (i.e., responses measured after infection) include: reduced antigen-specific IFN-gamma, iNOS, IL-4, and MIP1-alpha responses; reduced antigen-specific expansion of CD4+ T cells; and a diminished activation profile on T cells within antigen stimulated cultures. Delayed type hypersensitivity and IFN-gamma responses generally correlate with infection (i.e., diagnostic) but do not correlate with lesion severity. Comparative immunology studies including partnerships of researchers with veterinary and medical perspectives will continue to provide mutual benefit to TB research in man and animals.